Adoptive immunotherapy, using allogeneic lymphoid cells in combination with chemotherapy tumor cells in animal and human leukemias. The major obstacle confronting the use of allogeneic lymphoid grafts, even in HL-A compatible combinations, is the graft-versus-host (GVH) reaction. We are proposing a novel approach to the GVH problem which may be applicable to man. This approach is based on the recently established principal that rodent lymph nodes and spleens challenged by a specific antigen can selectively trap recirculating lymphocytes with specific reactivity to that antigen. We propose to use this principle to eliminate specific GVH reactivity to the recipient's histocompatibility antigens (H-antigens) from the donor's marrow. The immediate objectives of this proposed research are to continue and expand these studies by defining the optimal conditions for treating the donors so as to trap the maximum number of immunospecific lymphocytes, to use these conditions to deplete the donor's marrow of immunospecific GVH reactivity as defined by the popliteal lymph node GVH and GVH mortality assays and to then use this GVH depleted marrow in combination with chemotherapy to treat several models of mouse leukemia. The long-term objectives of these studies will be to then apply these methods to other mammaliam models and eventually to man.